Age increases expression and receptor-mediated activation of G alpha i in human atria.

Published

Journal Article

Recently, we demonstrated that beta2AR and several other Galphas-coupled receptors in human atria also couple to Galphai, a G protein that inhibits adenylyl cyclase (AC). The present study was undertaken to determine whether age increases expression of Galphai in human atrium, and more specifically whether it results in an increase in receptor-mediated activation of Galphai. Right atrial appendages were obtained from 14 mature adult (40-55 years) and 14 elderly (71-79 years) patients undergoing cardiac surgery. Immunoblotting of atrial membranes indicates that elderly atria have 82 +/- 18% more Galphai2 than atria from mature adults (P < 0.002); this increase in Galphai with age is confirmed by pertussis toxin-catalyzed ADP-ribosylation as well as by photoaffinity labeling with [32P]azidoanilido-GTP. We also find that receptor-mediated activation of Galphai is greater in elderly atria and that both basal and receptor-mediated AC activities decrease in elderly atria. These decreases in AC activity can be reversed by disabling Galphai with pertussis toxin, indicating that the age-dependent increases in Galphai expression and activation have functional consequences. Because beta2ARs in human atria mediate contractility through cAMP-mediated phosphorylation of phospholamban, we conclude that an age-induced increase in Galphai may have a role in depressing cardiac function in aged human atria.

Full Text

Duke Authors

Cited Authors

  • Kilts, JD; Akazawa, T; El-Moalem, HE; Mathew, JP; Newman, MF; Kwatra, MM

Published Date

  • November 2003

Published In

Volume / Issue

  • 42 / 5

Start / End Page

  • 662 - 670

PubMed ID

  • 14576516

Pubmed Central ID

  • 14576516

International Standard Serial Number (ISSN)

  • 0160-2446

Digital Object Identifier (DOI)

  • 10.1097/00005344-200311000-00013

Language

  • eng

Conference Location

  • United States